ALTERED SEROTONIN SYNTHESIS IN THE DENTATOTHALAMOCORTICAL PATHWAY IN AUTISTIC BOYS

Based on reports of increased platelet serotonin in 30 to 50% of autis tic subjects, abnormal serotonergic neurotransmission may be important in the pathogenesis of autism. However, serotonin metabolite measurem ents in cerebrospinal fluid of autistic subjects have failed to demons trate consistent abnormalities. Using alpha-[C-11]methyl-L-tryptophan as a tracer for serotonin synthesis with positron emission tomography, we now report unilateral alterations of serotonin synthesis in the de ntatothalamocortical pathway in autistic boys. Asymmetries of serotoni n synthesis were found in frontal cortex, thalamus, and dentate nucleu s of the cerebellum in all 7 boys, but not in the 1 autistic girl stud ied Decreased serotonin synthesis was found in the left frontal cortex and thalamus in 5 of the 7 boys and in the right frontal cortex and t halamus in the 2 remaining autistic boys. In all 7 cases, elevated ser otonin synthesis in the contralateral dentate nucleus was observed. St atistically significant differences between autistic boys and their no nautistic siblings (n = 5) were obtained when comparing asymmetry indi ces for frontal cortex, thalamus, and dentate nucleus combined as well as individually for frontal cortex and thalamus. These serotonergic a bnormalities in a brain pathway, important for language production and sensory integration, may represent one mechanism underlying the patho physiology of autism.